Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05061-x
Background Osteoporosis (OP) is a systemic bone disease characterized by damage to bone strength, leading to increased bone fragility and fracture risk. Cadherin 19 (CDH19) is located on chromosomes 18q22-q23, and 18q deletion is associated with terminal deletion diseases, including foot/hand deformities. However, the role of CDH19 in bone remains undefined. Methods A conditional knockout mouse model of the CDH19 gene was constructed using the Cre-loxP system, and the bone mass and bone morphology in mice were investigated using microCT and histological staining. Osteoblasts were isolated and cultured from wild-type and CDH19 knockout mice. Cell proliferation and differentiation were explored through EdU labeling, qPCR, alkaline phosphatase (ALP)/ alizarin red S (ARS) staining, and Western blot assays. The expression of genes altered in CDH19 gene knockout osteoblast was checked by RNA sequencing (RNA-seq), and subsequently confirmed by immunofluorescence and Western blot. Results We found that CDH19 could maintain the normal proliferation and differentiation in osteoblasts. After knocking out the CDH19 gene, the abilities of proliferation and osteogenesis were significantly inhibited in osteoblasts. Moreover, the bone mass of CDH19 knockout mice was significantly reduced, characterized by decreases in bone density, trabecular number, and bone volume fraction. The RNAseq analysis and western blot showed the PI3K/AKT signaling pathway was significantly inhibited in osteoblasts with CDH19 deletion. Furthermore, we demonstrated that administration of PI3K/AKT signaling pathway agonist 740Y-P partially alleviated the inhibition of osteogenic differentiation caused by CDH19 deletion in vitro and in vivo. Conclusion This study demonstrated that CDH19 regulated osteogenic differentiation by modulating the PI3K/AKT signaling pathway in osteoblasts. CDH19 may become a novel target for the treatment of bone diseases.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025047
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a complex pathogenesis that was previously thought to involve primarily adaptive immunity. Emerging evidence underscores the role of neutrophils in shaping immune dysregulation and inducing organ damage in lupus. This study aims to investigate the dynamics of neutrophil senescence and its relationship with lupus, an area that remains poorly understood. Here, we identify a significantly elevated proportion of CXCR4hiCD62Llo senescence-like neutrophils in the peripheral blood of SLE patients compare to that in the healthy donors. Increased numbers of senescence-like neutrophils are positively correlated with SLE disease activity and autoantibody production in SLE patients. In addition, senescence-like neutrophils derived from SLE patients exhibit an impaired ability to suppress the proinflammatory activity of natural killer (NK) cells and CD4+ T cells. Further mechanistic exploration suggests that these senescence-like neutrophils might exert their immunosuppressive effects via reactive oxygen species (ROS) production under physiological conditions. Our results demonstrate that senescence-like neutrophils could serve as biomarkers for assessing the disease activity of SLE. The compromised immunosuppressive function of senescence-like neutrophils provides a new perspective on SLE pathophysiology and may pave the way for the development of novel therapies.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05061-x
Osteoporosis is characterized by impaired bone formation relative to resorption, yet the molecular drivers of osteoblast dysfunction remain incompletely defined. Cadherin 19 (CDH19), located at chromosome 18q22-q23, has been linked to 18q deletion syndromes presenting with skeletal deformities, but its role in bone homeostasis was previously unknown. Using a Cre-loxP conditional knockout model, we demonstrate that CDH19 deletion in mice significantly reduces bone mass, with decreases in bone density, trabecular number, and bone volume fraction. Osteoblasts isolated from CDH19 knockout mice exhibit suppressed proliferation and osteogenic differentiation, as evidenced by EdU labeling, qPCR, alkaline phosphatase and alizarin red S staining, and Western blot. RNA sequencing and subsequent immunofluorescence and Western blot analyses reveal that the PI3K/AKT signaling pathway is markedly inhibited in CDH19-deficient osteoblasts. Administration of the PI3K/AKT agonist 740Y-P partially rescues the osteogenic differentiation deficit both in vitro and in vivo. These findings establish CDH19 as a critical regulator of osteoblast function through PI3K/AKT signaling and identify it as a potential therapeutic target for bone diseases such as osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21474
BACKGROUND: The tendon suturing technique for the hand has been continuously innovated with the development of biomechanics, minimally invasive techniques, and regenerative medicine. Over the past two decades, research has focused on optimizing traditional suturing techniques and the application of new repair materials, improving the effectiveness of tendon repair and the level of functional recovery in the hand. OBJECTIVE: To assess the global research status and development trends of hand tendon repair techniques over the past two decades through bibliometric analysis, identify research hotspots and their evolution. METHODS: Relevant literature was selected from the Web of Science database from 2005 to 2024, and bibliometric methods were employed for analysis. Data were organized using Microsoft Excel and analyzed for publication trends using the R language Bibliometrix package. VOSviewer was used to visualize keyword co-occurrence and collaboration networks, while CiteSpace was utilized to identify research hotspots and their temporal evolution. RESULTS AND CONCLUSION: Over the past two decades, research in the field of tendon suturing has shown a fluctuating growth trend. The United States, China, and Europe are the main contributing countries, with the United States occupying a central position in the global research network. Research on flexor tendon repair mainly focuses on biomechanics and the development of new repair materials, while extensor tendon research emphasizes postoperative functional recovery and complex injury repair. In recent years, biomaterials and regenerative medicine have gradually become research hotspots, promoting the application of precision medicine in tendon repair. In the future, interdisciplinary collaboration and the combination of advanced materials will further optimize hand tendon repair techniques.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025047
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex pathogenesis historically attributed to adaptive immunity. Emerging data implicate neutrophils in immune dysregulation and organ damage. This study investigates neutrophil senescence dynamics in SLE. We identified a significantly elevated proportion of CXCR4hiCD62Llo senescence-like neutrophils in peripheral blood of SLE patients versus healthy donors. Increased senescence-like neutrophil numbers positively correlated with SLE disease activity and autoantibody production. Functionally, senescence-like neutrophils from SLE patients exhibited impaired suppression of proinflammatory activity in natural killer (NK) cells and CD4+ T cells. Mechanistically, these cells may exert immunosuppressive effects via reactive oxygen species (ROS) production under physiological conditions. Our results position senescence-like neutrophils as candidate biomarkers for SLE disease activity. The compromised immunosuppressive function of these cells offers a new perspective on SLE pathophysiology and may inform development of novel therapies. Limitations include small sample size and heterogeneous treatment backgrounds, necessitating further validation. Future studies will address NET release and potential subset markers.